tbuckley/cabot-search huggingface dataset:
Efficacy and safety of emapalumab in macrophage activation syndrome
Authors: Fabrizio De Benedetti, Alexei A Grom, Paul A Brogan, Claudia Bracaglia, Manuela Pardeo, Giulia Marucci, Despina Eleftheriou, Charalampia Papadopoulou, Grant S Schulert, Pierre Quartier, Jordi Antón, Christian Laveille, Rikke Frederiksen, Veronica Asnaghi, Maria Ballabio, Philippe Jacqmin, Cristina de Min
Journal: Annals of the Rheumatic Diseases (2023)

Macrophage activation syndrome (MAS) is a severe, life-threatening complication of systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD). The objective of this study was to confirm the adequacy of an emapalumab dosing regimen in relation to interferon-γ (IFNγ) activity by assessing efficacy and safety. The efficacy outcome was MAS remission by week 8, based on clinical and laboratory criteria.
IL-37 Attenuates Platelet Activation and Thrombosis Through IL-1R8 Pathway
Authors: Yufei Chen, Jin Hong, Haoxuan Zhong, Yikai Zhao, Jian Li, Wei Shen, Xinping Luo, Haiming Shi, Liang Hu, Junling Liu, Wen Gao
Journal: Circulation Research (2023)

IL-37 (interleukin-37), a natural suppressor of innate inflammatory and immune responses, is increased in patients with myocardial infarction. Platelets play an important role in the progress of myocardial infarction, but the direct effects of IL-37 on platelet activation and thrombosis, as well as the underlying mechanisms, still remain unclear.We evaluated the direct effects of IL-37 on agonists-induced platelet activation and thrombus formation, as well as revealed the underlying mechanisms using platelet-specific IL-1R8 (IL-1 receptor 8)-deficient mice. Using myocardial infarct model, we explored the effects of IL-37 on microvascular obstruction and myocardial injury.IL-37 directly inhibited agonists-induced platelet aggregation, dense granule ATP release, P-selectin exposure, integrin αIIbβ3 activation, platelet spreading, and clot retraction. IL-37 inhibited thrombus formation in vivo in a FeCl3-injured mesenteric arteriole thrombosis mouse model and ex vivo in a microfluidic whole-blood perfusion assay. Mechanistic studies using platelet-specific IL-1R8-deficient mice revealed that IL-37 bound to platelet IL-1R8 and IL-18Rα, and IL-1R8 deficiency impaired the inhibitory effects of IL-37 on platelet activation. Using PTEN (phosphatase and tensin homolog)-specific inhibitor and PTEN-deficient platelets, we found that IL-37 combined with IL-1R8 to enhance PTEN activity, inhibit Akt (protein kinase B), mitogen-activated protein kinases, and spleen tyrosine kinase pathways, as well as decrease the generation of reactive oxygen species to regulate platelet activation. Exogenous IL-37 injection suppressed microvascular thrombosis to protect against myocardial injury in wild-type mice but not in platelet-specific IL-1R8-deficient mice after permanent ligation of the left anterior descending coronary. Finally, a negative correlation between plasma IL-37 concentration and platelet aggregation was observed in patients with myocardial infarction.IL-37 directly attenuated platelet activation, thrombus formation, and myocardial injury via IL-1R8 receptor. Accumulated IL-37 in plasma inhibited platelet activation to ameliorate atherothrombosis and infarction expansion, and thus may have therapeutic advantages as potential antiplatelet drugs.
Screening for fibrosis to diagnose liver diseases early: the LIVERSCREEN project
Authors: Pere Ginès, Maja Thiele, Isabel Graupera, Miquel Serra-Burriel, Robert J. de Knegt, Frank Lammert, Laurent Castera, Marko Korenjak, Patrick S. Kamath, Ivica Grgurević, Salvatore Piano, Núria Fabrellas, Anita Arslanow, Aleksander Krag
Journal: Nature Medicine (2023)
Epigenomic machinery regulating pediatric AML: Clonal expansion mechanisms, therapies, and future perspectives
Authors: Ugo Chianese, Chiara Papulino, Wout Megchelenbrink, Francesco Paolo Tambaro, Fortunato Ciardiello, Rosaria Benedetti, Lucia Altucci
Journal: Seminars in Cancer Biology (2023)

Acute myeloid leukemia (AML) is a heterogeneous disease with a genetic, epigenetic, and transcriptional etiology mainly presenting somatic and germline abnormalities. AML incidence rises with age but can also occur during childhood. Pediatric AML (pAML) accounts for 15–20% of all pediatric leukemias and differs considerably from adult AML. Next-generation sequencing technologies have enabled the research community to "paint" the genomic and epigenomic landscape in order to identify pathology-associated mutations and other prognostic biomarkers in pAML. Although current treatments have improved the prognosis for pAML, chemoresistance, recurrence, and refractory disease remain major challenges. In particular, pAML relapse is commonly caused by leukemia stem cells that resist therapy. Marked patient-to-patient heterogeneity is likely the primary reason why the same treatment is successful for some patients but, at best, only partially effective for others. Accumulating evidence indicates that patient-specific clonal composition impinges significantly on cellular processes, such as gene regulation and metabolism. Although our understanding of metabolism in pAML is still in its infancy, greater insights into these processes and their (epigenetic) modulation may pave the way toward novel treatment options. In this review, we summarize current knowledge on the function of genetic and epigenetic (mis)regulation in pAML, including metabolic features observed in the disease. Specifically, we describe how (epi)genetic machinery can affect chromatin status during hematopoiesis, leading to an altered metabolic profile, and focus on the potential value of targeting epigenetic abnormalities in precision and combination therapy for pAML. We also discuss the possibility of using alternative epidrug-based therapeutic approaches that are already in clinical practice, either alone as adjuvant treatments and/or in combination with other drugs.
Virological characterization of treatment failures and retreatment outcomes in patients infected with “unusual” HCV genotype 1 subtypes
Authors: Erwan Vo-Quang, Alexandre Soulier, Mélissa Ndebi, Christophe Rodriguez, Stéphane Chevaliez, Vincent Leroy, Slim Fourati, Jean-Michel Pawlotsky
Journal: Hepatology (2023)

Background and Aims: Suboptimal rates of sustained virological response have been reported in patients infected with an “unusual,” non-1a/1b HCV genotype 1 subtype. The objectives of this study were to assess the proportion of non-1a/1b genotype 1 subtypes in a population of HCV-infected patients who failed to achieve sustained virological response after first-line direct-acting antiviral treatment, to virologically characterize their failures and to assess their outcomes on retreatment. Approach and Results: Samples addressed between January 2015 and December 2021 to the French National Reference Center for Viral Hepatitis B, C, and D were prospectively analyzed by means of Sanger and deep sequencing. Among 640 failures, 47 (7.3%) occurred in patients infected with an “unusual” genotype 1 subtype. Samples were available in 43 of them; 92.5% of these patients were born in Africa. Our results show the presence at baseline and at treatment failure of NS3 protease and/or NS5A polymorphisms conferring inherent reduced susceptibility to direct-acting antivirals in these patients, together with the presence at failure of additional resistance-associated substitutions not naturally present as dominant species, but jointly selected by first-line therapy. Conclusions: Patients infected with “unusual” HCV genotype 1 subtypes are over-represented among direct-acting antiviral treatment failures. Most of them were born and likely infected in sub-Saharan Africa. “Unusual” HCV genotype 1 subtypes naturally carry polymorphisms that confer reduced susceptibility to the drugs currently used to cure hepatitis C, in particular the NS5A inhibitors. Retreatment with sofosbuvir plus an NS3 protease and an NS5A inhibitor is generally efficacious.
Preoperative volume of the optic chiasm is an easily obtained predictor for visual recovery of pituitary adenoma patients following endoscopic endonasal transsphenoidal surgery: a cohort study
Authors: Yang Zhang, Chaoyue Chen, Wei Huang, Yuen Teng, Xin Shu, Fumin Zhao, Jianguo Xu, Lei Zhang
Journal: International Journal of Surgery (2023)

Predicting the postoperative visual outcome of pituitary adenoma patients is important but remains challenging. This study aimed to identify a novel prognostic predictor which can be automatically obtained from routine MRI using a deep learning approach.A total of 220 pituitary adenoma patients were prospectively enrolled and stratified into the recovery and nonrecovery groups according to the visual outcome at 6 months after endoscopic endonasal transsphenoidal surgery. The optic chiasm was manually segmented on preoperative coronal T2WI, and its morphometric parameters were measured, including suprasellar extension distance, chiasmal thickness, and chiasmal volume. Univariate and multivariate analyses were conducted on clinical and morphometric parameters to identify predictors for visual recovery. Additionally, a deep learning model for automated segmentation and volumetric measurement of optic chiasm was developed with nnU-Net architecture and evaluated in a multicenter data set covering 1026 pituitary adenoma patients from four institutions.Larger preoperative chiasmal volume was significantly associated with better visual outcomes ( P =0.001). Multivariate logistic regression suggested it could be taken as the independent predictor for visual recovery (odds ratio=2.838, P <0.001). The auto-segmentation model represented good performances and generalizability in internal (Dice=0.813) and three independent external test sets (Dice=0.786, 0.818, and 0.808, respectively). Moreover, the model achieved accurate volumetric evaluation of the optic chiasm with an intraclass correlation coefficient of more than 0.83 in both internal and external test sets.The preoperative volume of the optic chiasm could be utilized as the prognostic predictor for visual recovery of pituitary adenoma patients after surgery. Moreover, the proposed deep learning-based model allowed for automated segmentation and volumetric measurement of the optic chiasm on routine MRI.
HSR23-090: Racial Differences in Outcomes of Osimertinib in Patients With EGFR-Positive Non–Small Cell Lung Cancer in a Real World US Population
Authors: Jeffrey Zhong, Jaime Abe Perez, Annie Liang Zhang, Debora Bruno, Melinda Laine-Hsu
Journal: Journal of the National Comprehensive Cancer Network (2023)

"HSR23-090: Racial Differences in Outcomes of Osimertinib in Patients With EGFR-Positive Non–Small Cell Lung Cancer in a Real World US Population" published on 31 Mar 2023 by National Comprehensive Cancer Network.
CLO23-053: Update From the Dedalo Protocol: An Integrated Approach to MRD in CLL Patients Receiving Venetoclax Plus Rituximab
Authors: Fabrizio Mavilia, Francesco Ghio, Giulia Cervetti, Claudia Baratè, Gaspare Tandredi, Dimitri Dardanis, Elisa Mazzantini, Pietro Rossi, Paola Sammuri, Valentina Guerri, Clara Bono, Susanna Grassi, Edoardo Benedetti, Sara Galimberti
Journal: Journal of the National Comprehensive Cancer Network (2023)
Adding Inflammatory Markers and Refining National Institute on Alcohol Abuse and Alcoholism Criteria Improve Diagnostic Accuracy for Alcohol-associated Hepatitis
Authors: Emma Avitabile, Alba Díaz, Carla Montironi, Martina Pérez-Guasch, Jordi Gratacós-Ginès, Helena Hernández-Évole, Roger K. Moreira, Tejasav S. Sehrawat, Harmeet Malhi, Pol Olivas, Virginia Hernández-Gea, Ramón Bataller, Vijay H. Shah, Patrick S. Kamath, Pere Ginès, Elisa Pose
Journal: Clinical Gastroenterology and Hepatology (2023)
CLO23-058: Targeted Axillary Dissection Post Primary Chemotherapy: Data Analysis From a Single Multidisciplinary Unit in South Africa
Authors: Carol-Ann Benn, Bernado Rapoport, Dominic van Loggerenberg
Journal: Journal of the National Comprehensive Cancer Network (2023)

"CLO23-058: Targeted Axillary Dissection Post Primary Chemotherapy: Data Analysis From a Single Multidisciplinary Unit in South Africa" published on 31 Mar 2023 by National Comprehensive Cancer Network.
YIA23-002: Evolutionary Pressures Shape Soft Tissue Sarcoma Development and Response to Radiotherapy
Authors: Erik S. Blomain, Anish Somani, Ajay Subramanian, Shaghayegh Soudi, Eniola Oladipo, Christin New, Deborah E. Kenney, Neda Nemat-Gorgani, Susan M. Hiniker, Alexander L. Chin, Raffi S. Avedian, Robert J. Steffner, David G. Mohler, Matt van de Rijn, Everett Moding
Journal: Journal of the National Comprehensive Cancer Network (2023)
GFR, Race, and Implications
Authors: David Goldsmith
Journal: Journal of the American Society of Nephrology (2023)

The latest JASN features a very important submission, by a distinguished authorial roster, concerning the altered clinical use and outcomes once race-independent GFR values are used instead of those derived from Chronic Kidney Disease Epidemiology Collaboration and even more antique formulas.1 This excellent review,1 which signposts important possibly life-altering changes in the way that GFR will be applied to patients of all races, carries a serious and troubling statement, namely "A national task force convened by the NKF-ASN2 recently recommended a new race-free creatinine equation for calculating eGFR…its broad effect on recommended clinical care across the eGFR spectrum and across different racial and ethnic groups is not known." That statement is remarkable as presented, as surely thorough modeling of the clinical impact of such a fundamental change must have been undertaken before, and not after, these changes were adopted. In the event, the new analysis1 suggests that nationwide implementation of the new eGFR equation may affect recommended care for 100,000s of Black adults and 1,000,000s of non-Black adults, including altered CKD diagnoses; CKD stage reclassifications; and changes in kidney donation eligibility, nephrologist referral, and medication dosing. These are dramatic alterations for a sizable number of patients, as presaged by others.3,4 How confident are the authors that medication dosing will potentially be altered for drugs which include but are not limited to beta-blockers, Sodium-Glucose Cotransporter-2 inhibitor, statins, antibiotics, etc? For such medications to be effective at preventing CKD progression and cardiovascular disease, and to reduce the risk of toxicity, it is surely incumbent to use them based on consistent and patient-specific GFR measurements? Is it also correct to encourage medication changes to be made to individual patients in large sections of the population based solely on the use of the imprecise population-derived eGFR formulas currently available to clinicians? Disclosures None. Funding None.
CLO23-036: A Rare Case of Intratubular Cytoplasmic AL Amyloidosis in a Patient Without Multiple Myeloma
Authors: Sarah Khan, Vijay Ketan Reddy, Ekaterina Proskuriakova, Pam Khosla, Shan-Ching Ying, Haoliang Xu
Journal: Journal of the National Comprehensive Cancer Network (2023)
CLO23-063: Impact of Socio-Economic Disparity on Survival of HER 2 Neu (+) Breast Cancer Brain Metastasis Patients With Chemotherapy: A SEER Study
Authors: Akhil Jain, Rikeen Dhaduk, Sagar Patel, Udhayvir Singh Grewal
Journal: Journal of the National Comprehensive Cancer Network (2023)

"CLO23-063: Impact of Socio-Economic Disparity on Survival of HER 2 Neu (+) Breast Cancer Brain Metastasis Patients With Chemotherapy: A SEER Study" published on 31 Mar 2023 by National Comprehensive Cancer Network.
EPR23-085: Prevalence of Substance Use in Cancer Patients at a 5-Year Difference: A Cross-Sectional Study From Nationally Representative Population
Authors: Akhil Jain, Sabah Iqbal, Sohiel Deshpande, Krishna Desai, Aisha Sultana, Kristal Pereria, Monika Garg, Bohdan Baralo, Rajesh Thirumaran
Journal: Journal of the National Comprehensive Cancer Network (2023)

"EPR23-085: Prevalence of Substance Use in Cancer Patients at a 5-Year Difference: A Cross-Sectional Study From Nationally Representative Population" published on 31 Mar 2023 by National Comprehensive Cancer Network.
YIA23-006: BE-EPIC: Behavioral Economic Interventions to Embed Palliative Care in Community Oncology
Authors: Ravi B. Parikh, Ramy Sedhom, William J. Ferrell, Katherine Villarin, Kara Berwanger, Bethann Scarborough, Randall Oyer, Pallavi Kumar, Niharika Ganta, Shanthi Sivendran, Jinbo Chen, Kevin G. Volpp, Justin E. Bekelman
Journal: Journal of the National Comprehensive Cancer Network (2023)
CLO23-054: The Role of miRNA 21 and miRNA 101 in Diagnosis, Prognosis and Survival of Laryngeal Cancer
Authors: Begum Bahar Yilmaz, Sinem Durmus, Yetkin Zeki Yilmaz, Murat Yener, Irfan Papila, Hafize Uzun
Journal: Journal of the National Comprehensive Cancer Network (2023)
When I use a word . . . .Devising bioscience definitions
Authors: Jeffrey K Aronson
Journal: BMJ (2023)

Lexicographers’ jobs include crafting definitions of words, a task that is not as easy as many think it is. To do this, one can call on four methods, alone or more often in combination, based on etymology, usages, previous definitions, and the Ramsay–Lewis method, in which a term or group of terms appearing in a theory can be defined implicitly by the assertions of the theory itself. Terms that I have defined using some or all of these methods include adherence to medications; adverse drug reactions and related terms; artificial intelligence; bias; biomarkers; complex systematic reviews; drug shortages; medical devices; medication errors; me-too pharmaceutical products; nutraceuticals; pharmacological mechanisms; the Precautionary Principle; rapid reviews; research and translational research; rewardable innovation and innovativeness in drug therapy; signals in pharmacovigilance; surveillance of the effects of drug therapy; unlicensed and off-label uses of medicines. Some of these definitions have been adopted internationally.
QIM23-130: Committing to Resiliency: Transforming Burnout to Resilience at a National Cancer Institute (NCI) Comprehensive Cancer Center
Authors: Amy Gallagher, Amy Case
Journal: Journal of the National Comprehensive Cancer Network (2023)

"QIM23-130: Committing to Resiliency: Transforming Burnout to Resilience at a National Cancer Institute (NCI) Comprehensive Cancer Center" published on 31 Mar 2023 by National Comprehensive Cancer Network.
Validation of a Hypoglycemia Risk Stratification Tool Using Data From Continuous Glucose Monitors
Authors: Andrew J. Karter, Melissa M. Parker, Howard H. Moffet, Kasia J. Lipska, James D. Ralston, Elbert S. Huang, Lisa K. Gilliam
Journal: JAMA Network Open (2023)

This cohort study uses data from continuous glucose monitoring to validate a hypoglycemia risk stratification tool.
Hyper‐inflammation and complement in <scp>COVID</scp>‐19
Authors: Bruno G. Pires, Rodrigo T. Calado
Journal: American Journal of Hematology (2023)

Abstract COVID‐19 is a complex disease manifesting in a broad severity spectrum and involving distinct organs and systems. Hyperinflammation, including complement over‐activation, has a pivotal role in severe COVID‐19 pathobiology, stimulating the inflammatory response, causing microangiopathy, platelet–neutrophil activation, and hypercoagulability. SARS‐CoV‐2 can directly activate the complement system by the classic, alternative, and lectin pathways, and infected cells can produce intracellular complement (the complesome). COVID‐19 severity appears to be associated with the degree of complement activation, and it has been hypothesized that patients with COVID‐19 may benefit from therapeutic complement inhibition. Different complement cascade molecules may be targeted with potential advantages and disadvantages. Which target(s) is the most effective and when is the best timing for intervention remain open questions. Early phase I and phase II clinical trials have shown promising but conflicting results, warranting phase III controlled randomized trials. Upstream complement inhibition appears to better and more effectively block hyperinflammation with potential clinical significance. Understanding how SARS‐CoV‐2 exploits the complement system can add precious information about the pathogenesis of other infections, inflammatory, and autoimmune diseases beyond COVID‐19.
Phenotypes Associated With Zones Defined by Area Under the Curve Glucose and C-peptide in a Population With Islet Autoantibodies
Authors: Jay M. Sosenko, David Cuthbertson, Emily K. Sims, Heba M. Ismail, Brandon M. Nathan, Laura M. Jacobsen, Mark A. Atkinson, Carmella Evans-Molina, Kevan C. Herold, Jay S. Skyler, Maria J. Redondo
Journal: Diabetes Care (2023)

Metabolic zones were developed to characterize heterogeneity of individuals with islet autoantibodies.
CLO23-043: Optimal Interval Between Immune Therapy and Targeted Therapy With Sotorasib in Patients With KRAS G12C Mutant Non–Small Cell Lung Cancer
Authors: Julia Bielanin, Wade T. Iams, Heidi Chen, Amanda Cass
Journal: Journal of the National Comprehensive Cancer Network (2023)

"CLO23-043: Optimal Interval Between Immune Therapy and Targeted Therapy With Sotorasib in Patients With KRAS G12C Mutant Non–Small Cell Lung Cancer" published on 31 Mar 2023 by National Comprehensive Cancer Network.
PCL23-125: Volatile Organic Compounds Released by Gastric Tissues as Potential Biomarkers of Gastric Cancer
Authors: Veronika Patsko, Pawel Mochalski, Marcis Leja, Andrii Lukashenko, Daria Ślefarska-Wolak, Linda Mezmale, Clemens Ager, Agnieszka Królicka, Chris A. Mayhew, Gidi Shani, Hossam Haick
Journal: Journal of the National Comprehensive Cancer Network (2023)
CLO23-038: The Impact of Dysbiosis Agents on the Effectiveness of Immune Checkpoint Inhibitors in Advanced Melanoma Patients: A Systematic Review With Meta-Analysis
Authors: Chin-Hsuan Huang, Andrea S. Porpiglia, Yi-No Kang, Yu Chang, Tsu-Hsien Wang, Kuan-Yu Chi
Journal: Journal of the National Comprehensive Cancer Network (2023)

"CLO23-038: The Impact of Dysbiosis Agents on the Effectiveness of Immune Checkpoint Inhibitors in Advanced Melanoma Patients: A Systematic Review With Meta-Analysis" published on 31 Mar 2023 by National Comprehensive Cancer Network.
CLO23-030: MC200402-Single-Arm Phase 2 Study of the FGFR Inhibitor Futibatinib (Futi) in Combination With Pembrolizumab (Pem) in Patients With FGF19 Expressing Advanced or Metastatic Hepatocellular Carcinoma (aHCC)
Authors: Nguyen H. Tran, Joseph J Larson, Fang-Shu Ou, Amit Mahipal, Shaylene A. McCue, Rondell P. Graham, Martin E. Fernandez-Zapico, Alexander Revzin, Lionel A. Kankeu Fonkoua, Lynn M. Flickinger, Sean P. Cleary, Tanios S. Bekaii-Saab, Mitesh J. Borad, Robert R. McWilliams, Aminah Jatoi, Wen Wee Ma
Journal: Journal of the National Comprehensive Cancer Network (2023)

"CLO23-030: MC200402-Single-Arm Phase 2 Study of the FGFR Inhibitor Futibatinib (Futi) in Combination With Pembrolizumab (Pem) in Patients With FGF19 Expressing Advanced or Metastatic Hepatocellular Carcinoma (aHCC)" published on 31 Mar 2023 by National Comprehensive Cancer Network.
QIM23-140: Health Care Satisfaction Among Cancer Patients Undergoing Radiotherapy: A Tunisian Center Experience
Authors: Haifa Haj Abdallah, Sabrine Tbessi, Emna Boudhina, Rym Zanzouri, Samia Belaajouza, Nadia Bouzid, Sameh Tebra
Journal: Journal of the National Comprehensive Cancer Network (2023)
BIO23-023: Supporting the Capture of Structured Data for Patients With Cancer Using Cancer-Specific Note Templates
Authors: Hamid Emamekhoo, Cibele Carroll, Chelsea Stietz, Jeffrey B. Pier, Michael D. Lavitschke, Daniel Mulkerin, Mary E. Sesto, Amye J. Tevaarwerk
Journal: Journal of the National Comprehensive Cancer Network (2023)